tbuckley/cabot-search huggingface dataset:
CEACAM6 as a Novel Therapeutic Target to Boost HO-1—mediated Antioxidant Defense in COPD
Authors: Cheng-Yu Wu, Anis Cilic, Oleg Pak, Ruth Charlotte Dartsch, Jochen Wilhelm, Magdalena Wujak, Kevin Lo, Monika Brosien, Ruoyu Zhang, Ibrahim Alkoudmani, Biruta Witte, Frauke Pedersen, Henrik Watz, Robert Voswinckel, Andreas Günther, Hossein A. Ghofrani, Ralf P. Brandes, Ralph T. Schermuly, Friedrich Grimminger, Werner Seeger, Natascha Sommer, Norbert Weissmann, Stefan Hadzic
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

Rationale: Tobacco smoking and air pollution are primary causes of chronic obstructive pulmonary disease (COPD). However, only a minority of smokers develop COPD. The mechanisms underlying the defense against nitrosative/oxidative stress in nonsusceptible smokers to COPD remain largely unresolved. Objectives: To investigate the defense mechanisms against nitrosative/oxidative stress that possibly prevent COPD development or progression. Methods: Four cohorts were investigated: 1) sputum samples (healthy, n = 4; COPD, n = 37), 2) lung tissue samples (healthy, n = 13; smokers without COPD, n = 10; smoker+COPD, n = 17), 3) pulmonary lobectomy tissue samples (no/mild emphysema, n = 6), and 4) blood samples (healthy, n = 6; COPD, n = 18). We screened 3-nitrotyrosine (3-NT) levels, as indication of nitrosative/oxidative stress, in human samples. We established a novel in vitro model of a cigarette smoke extract (CSE)–resistant cell line and studied 3-NT formation, antioxidant capacity, and transcriptomic profiles. Results were validated in lung tissue, isolated primary cells, and an ex vivo model using adeno-associated virus-mediated gene transduction and human precision-cut lung slices. Measurements and Main Results: 3-NT levels correlate with COPD severity of patients. In CSE-resistant cells, nitrosative/oxidative stress upon CSE treatment was attenuated, paralleled by profound upregulation of heme oxygenase-1 (HO-1). We identified carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) as a negative regulator of HO-1–mediated nitrosative/oxidative stress defense in human alveolar type 2 epithelial cells (hAEC2s). Consistently, inhibition of HO-1 activity in hAEC2s increased the susceptibility toward CSE-induced damage. Epithelium-specific CEACAM6 overexpression increased nitrosative/oxidative stress and cell death in human precision-cut lung slices on CSE treatment. Conclusions: CEACAM6 expression determines the hAEC2 sensitivity to nitrosative/oxidative stress triggering emphysema development/progression in susceptible smokers.
Transcatheter Mitral Valve Repair for Degenerative Mitral Regurgitation
Authors: Raj R. Makkar, Joanna Chikwe, Tarun Chakravarty, Qiudong Chen, Patrick T. O’Gara, Marc Gillinov, Michael J. Mack, Andrew Vekstein, Dhairya Patel, Amanda Lee Stebbins, Annetine C. Gelijns, Moody Makar, Deepak L. Bhatt, Samir Kapadia, Sreekanth Vemulapalli, Martin B. Leon
Journal: JAMA (2023)

Importance There are limited data on the outcomes of transcatheter edge-to-edge mitral valve repair for degenerative mitral regurgitation (MR) in a real-world setting. Objective To evaluate the outcomes of transcatheter mitral valve repair for degenerative MR. Design, Setting, and Participants Cohort study of consecutive patients in the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapies Registry who underwent nonemergent transcatheter mitral valve repair for degenerative MR in the US from 2014 through 2022. Exposure Transcatheter edge-to-edge mitral valve repair with the MitraClip device (Abbott). Main Outcomes and Measures The primary end point was MR success, defined as moderate or less residual MR and a mean mitral gradient of less than 10 mm Hg. Clinical outcomes were evaluated based on the degree of residual MR (mild or less MR or moderate MR) and mitral valve gradients (≤5 mm Hg or &amp;amp;gt;5 to &amp;amp;lt;10 mm Hg). Results A total of 19 088 patients with isolated moderate to severe or severe degenerative MR who underwent transcatheter mitral valve repair were analyzed (median age, 82 years; 48% women; median Society of Thoracic Surgeons predicted risk of mortality with surgical mitral valve repair, 4.6%). MR success was achieved in 88.9% of patients. At 30 days, the incidence of death was 2.7%; stroke, 1.2%; and mitral valve reintervention, 0.97%. MR success compared with an unsuccessful procedure was associated with significantly lower mortality (14.0% vs 26.7%; adjusted hazard ratio, 0.49; 95% CI, 0.42-0.56; P &amp;amp;lt; .001) and heart failure readmission (8.4% vs 16.9%; adjusted hazard ratio, 0.47; 95% CI, 0.41-0.54; P &amp;amp;lt; .001) at 1 year. Among patients with MR success, the lowest mortality was observed in patients who had both mild or less residual MR and mean mitral gradients of 5 mm Hg or less compared with those with an unsuccessful procedure (11.4% vs 26.7%; adjusted hazard ratio, 0.40; 95% CI, 0.34-0.47; P &amp;amp;lt; .001). Conclusions and Relevance In this registry-based study of patients with degenerative MR undergoing transcatheter mitral valve repair, the procedure was safe and resulted in successful repair in 88.9% of patients. The lowest mortality was observed in patients with mild or less residual MR and low mitral gradients.
Mirror, Mirror on the Wall: Do Kidney RCT Populations Represent the People We Treat?
Authors: Crystal A. Gadegbeku
Journal: Journal of the American Society of Nephrology (2023)

Department of Kidney Medicine, Cleveland Clinic, Cleveland, Ohio Correspondence: Dr. Crystal A. Gadegbeku Cleveland Clinic, Department of Kidney Medicine, 9500 Euclid Avenue/Q7 Cleveland, OH 44195. Email: [email protected] Published online ahead of print. Publication date available at www.jasn.org. See related article, "Representation of Racial and Ethnic Minorities in Nephrology Clinical Trials: A Systematic Review and Meta-Analysis," on pages 1167–1177.
Comparison of pulmonary congestion severity using artificial intelligence‐assisted scoring versus clinical experts: A secondary analysis of <scp>BLUSHED‐AHF</scp>
Authors: Andrew J. Goldsmith, Mike Jin, Ruben Lucassen, Nicole M. Duggan, Nicholas E. Harrison, William Wells, Robert R. Ehrman, Robinson Ferre, Luna Gargani, Vicki Noble, Phil Levy, Katie Lane, Xiaochun Li, Sean Collins, Peter Pang, Tina Kapur, Frances M. Russell
Journal: European Journal of Heart Failure (2023)
Ratiometric optical probes for biosensing
Authors: Xiao Yang, Congcong Li, Peifeng Li, Qinrui Fu
Journal: Theranostics (2023)

Biosensing by optical probes is bringing about a revolution in our understanding of physiological and pathological states.Conventional optical probes for biosensing are prone to inaccurate detection results due to various analyte-independent factors that can lead to fluctuations in the absolute signal intensity.Ratiometric optical probes provide built-in self-calibration signal correction for more sensitive and reliable detection.Probes specifically developed for ratiometric optical detection have been shown to significantly improve the sensitivity and accuracy of biosensing.In this review, we focus on the advancements and sensing mechanism of ratiometric optical probes including photoacoustic (PA) probes, fluorescence (FL) probes, bioluminescence (BL) probes, chemiluminescence (CL) probes and afterglow probes.The versatile design strategies of these ratiometric optical probes are discussed along with a broad range of applications for biosensing such as sensing of pH, enzymes, reactive oxygen species (ROS), reactive nitrogen species (RNS), glutathione (GSH), metal ions, gas molecules and hypoxia factors, as well as the fluorescence resonance energy transfer (FRET)-based ratiometric probes for immunoassay biosensing.Finally, challenges and perspectives are discussed.
Four-Year Visual Outcomes After Intravitreous Aflibercept for Vision-Threatening Complications of Diabetic Retinopathy
Authors: Piotr Kanclerz, Raimo Tuuminen
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<i>In vivo</i> imaging of CD8<sup>+</sup> T cells in metastatic cancer patients: first clinical experience with simultaneous [<sup>89</sup>Zr]Zr-Df-IAB22M2C PET/MRI
Authors: Johannes Schwenck, Dominik Sonanini, Dominik Seyfried, Walter Ehrlichmann, Gabriele Kienzle, Gerald Reischl, Pascal Krezer, Ian Wilson, Ron Korn, Irene Gonzalez-Menendez, Leticia Quintanilla-Martinez, Ferdinand Seith, Andrea Forschner, Thomas Eigentler, Lars Zender, Martin Röcken, Bernd J Pichler, Lukas Flatz, Manfred Kneilling, Christian la Fougere
Journal: Theranostics (2023)

Aim/Introduction: Despite the spectacular success of immune checkpoint inhibitor therapy (ICT) in patients with metastatic cancer, only a limited proportion of patients benefit from ICT. CD8 + cytotoxic T cells are important gatekeepers for the therapeutic response to ICT and are able to recognize MHC class I-dependent tumor antigens and destroy tumor cells.The radiolabeled minibody [ 89 Zr]Zr-Df-IAB22M2C has a high affinity for human CD8 + T cells and was successfully tested in a phase I study.Here, we aimed to gain the first clinical PET/MRI experience with the noninvasive assessment of the CD8 + T-cell distribution in cancer patients by in vivo [ 89 Zr]Zr-Df-IAB22M2C with a distinct focus of identifying potential signatures of successful ICT. Material and Methods:We investigated 8 patients with metastasized cancers undergoing ICT.Radiolabeling of Df-IAB22M2C with Zr-89 was performed according to Good Manufacturing Practice.Multiparametric PET/MRI was acquired 24 h after injection of 74.2±17.9MBq [ 89 Zr]Zr-Df-IAB22M2C.We analyzed [ 89 Zr]Zr-Df-IAB22M2C uptake within the metastases and within primary and secondary lymphatic organs.Results: [ 89 Zr]Zr-Df-IAB22M2C injection was tolerated well without noticeable side effects.The CD8 PET/MRI data acquisitions 24 hours post-administration of [ 89 Zr]Zr-Df-IAB22M2C revealed good image quality with a relatively low background signal due to only low unspecific tissue uptake and marginal blood pool retention.Only two metastatic lesions showed markedly increased tracer uptake in our cohort of patients.Furthermore, we observed high interpatient variability in [ 89 Zr]Zr-Df-IAB22M2C uptake within the primary and secondary lymphoid organs.Four out of five ICT patients exhibited rather high [ 89 Zr]Zr-Df-IAB22M2C uptake in the bone marrow.Two of these four patients as well as two other patients yielded pronounced [ 89 Zr]Zr-Df-IAB22M2C uptake within nonmetastatic lymph nodes.Interestingly, cancer progression in ICT patients was associated with a relatively low [ 89 Zr]Zr-Df-IAB22M2C uptake in the spleen compared to the liver in 4 out of the 6 patients.Lymph nodes with enhanced [ 89 Zr]Zr-Df-IAB22M2C uptake revealed significantly reduced apparent diffusion coefficient (ADC) values in diffusion weighted MRI.Conclusion: Our first clinical experiences revealed the feasibility of [ 89 Zr]Zr-Df-IAB22M2C PET/MRI in assessing potential immune-related changes in metastases and primary and secondary lymphatic organs.
The interplay between non-coding RNAs and alternative splicing: from regulatory mechanism to therapeutic implications in cancer
Authors: Min Liu, Subo Zhang, Heng Zhou, Xiaoyun Hu, Jianing Li, Boshi Fu, Minjie Wei, Huilin Huang, Huizhe Wu
Journal: Theranostics (2023)

Alternative splicing (AS) is a common and conserved process in eukaryotic gene regulation.It occurs in approximately 95% of multi-exon genes, greatly enriching the complexity and diversity of mRNAs and proteins.Recent studies have found that in addition to coding RNAs, non-coding RNAs (ncRNAs) are also inextricably linked with AS.Multiple different types of ncRNAs are generated by AS of precursor long non-coding (pre-lncRNAs) or precursor messenger RNAs (pre-mRNAs).Furthermore, ncRNAs, as a novel class of regulators, can participate in AS regulation by interacting with the cis-acting elements or trans-acting factors.Several studies have implicated abnormal expression of ncRNAs and ncRNA-related AS events in the initiation, progression, and therapy resistance in various types of cancers.Therefore, owing to their roles in mediating drug resistance, ncRNAs, AS-related factors and AS-related novel antigens may serve as promising therapeutic targets in cancer treatment.In this review, we summarize the interaction between ncRNAs and AS processes, emphasizing their great influences on cancer, especially on chemoresistance, and highlighting their potential values in clinical treatment.
Roles of glycosylation at the cancer cell surface: opportunities for large scale glycoproteomics
Authors: Tomislav Čaval, Frederico Alisson-Silva, Flavio Schwarz
Journal: Theranostics (2023)

Cell surface glycosylation has a variety of functions, and its dysregulation in cancer contributes to impaired signaling, metastasis and the evasion of the immune responses.Recently, a number of glycosyltransferases that lead to altered glycosylation have been linked to reduced anti-tumor immune responses: B3GNT3, which is implicated in PD-L1 glycosylation in triple negative breast cancer, FUT8, through fucosylation of B7H3, and B3GNT2, which confers cancer resistance to T cell cytotoxicity.Given the increased appreciation of the relevance of protein glycosylation, there is a critical need for the development of methods that allow for an unbiased interrogation of cell surface glycosylation status.Here we provide an overview of the broad changes in glycosylation at the surface of cancer cell and describe selected examples of receptors with aberrant glycosylation leading to functional changes, with emphasis on immune checkpoint inhibitors, growth-promoting and growth-arresting receptors.Finally, we posit that the field of glycoproteomics has matured to an extent where large-scale profiling of intact glycopeptides from the cell surface is feasible and is poised for discovery of new actionable targets against cancer.
PER2 integrates circadian disruption and pituitary tumorigenesis
Authors: Lianxia Guo, Haobin Cen, Jiaxian Weng, Yiting He, Xiaocao Guo, Di He, Kaisheng Liu, Shuyi Duan, Jing Yang, Xiaojian Zhang, Zifei Qin, Yong Wan, Zhiyong Chen, Baojian Wu
Journal: Theranostics (2023)

Rationale:The role of circadian clock in pituitary tumorigenesis remains elusive.Here we investigate whether and how circadian clock modulates the development of pituitary adenomas.Methods and Results: We found altered expression of pituitary clock genes in patients with pituitary adenomas.In particular, PER2 is prominently upregulated.Further, jetlagged mice with PER2 upregulation have accelerated growth of GH3 xenograft tumor.Conversely, loss of Per2 protects mice against developing estrogen-induced pituitary adenoma.Similar antitumor effect is observed for SR8278, a chemical that can decrease pituitary PER2 expression.RNA-seq analysis suggests involvement of cell cycle disturbance in PER2 regulation of pituitary adenoma.Subsequent in vivo and cell-based experiments validate that PER2 induces pituitary expression of Ccnb2, Cdc20 and Espl1 (three cell cycle genes) to facilitate cell cycle progression and inhibit apoptosis, thereby promoting pituitary tumorigenesis.Mechanistically, PER2 regulates the transcription of Ccnb2, Cdc20 and Espl1 through enhancing the transcriptional activity of HIF-1α.HIF-1α trans-activates Ccnb2, Cdc20 and Espl1 via direct binding to its specific response element in the gene promoters.Conclusion: PER2 integrates circadian disruption and pituitary tumorigenesis.These findings advance our understanding of crosstalk between circadian clock and pituitary adenomas and highlight the relevance of clock-based approaches in disease management.
Error in Byline, Affiliations, and Contributions
Journal: JAMA Network Open (2023)

Robyn Mitchell, MHSc; Joelle Cayen, BSc; Nisha Thampi, MD, MSc; Charles Frenette, MD; Jessica Bartoszko, HBSc; Kelly Baekyung Choi, MSc; Jeannette L. Comeau, MD, MSc; John Conly, MD; Chelsey Ellis, MD; Jennifer Ellison, MSc; John Embil, MD; Gerald Evans, MD; Lynn Johnston, MD, MSc; Jennie Johnstone, MD, PhD; Kevin C. Katz, MD, MSc; Pamela Kibsey, MD; Bonita Lee, MD, MSc (Epi); Marie-Astrid Lefebvre, MD, MSc; Yves Longtin, MD; Allison McGeer, MD, MSc; Dominik Mertz, MD, MSc; Jessica Minion, MD, MSc; Wallis Rudnick, PhD; Anada Silva, MPH; Stephanie W. Smith, MD, MSc; Jocelyn A. Srigley, MD, MSc; Kathryn N. Suh, MD, MSc; Jen Tomlinson, RN, BN, MHS; Alice Wong, MD, MPH; Linda Pelude, MSc
Tumor Microenvironment‐Responsive Hydrogel for Direct Extracellular ATP Imaging‐Guided Surgical Resection with Clear Boundaries
Authors: Jingyi Yang, Jiahao Qu, Xuanming Teng, Weiping Zhu, Yufang Xu, Yangyang Yang, Xuhong Qian
Journal: Advanced Healthcare Materials (2023)

Abstract Most solid tumors are clinically treated using surgical resection, and the presence of residual tumor tissues at the surgical margins often determines tumor survival and recurrence. Herein, a hydrogel (Apt‐HEX/Cp‐BHQ1 Gel, termed AHB Gel) is developed for fluorescence‐guided surgical resection. AHB Gel is constructed by tethering a polyacrylamide hydrogel and ATP‐responsive aptamers together. It exhibits strong fluorescence under high ATP concentrations corresponding to the TME (100–500 µ m ) but shows little fluorescence at low ATP concentrations (10–100 n m ) such as those in normal tissues. AHB Gel can rapidly (within 3 min) emit fluorescence after exposure to ATP, and the fluorescence signal only occurs at sites exposed to high ATP, resulting in a clear boundary between the ATP‐high and ATP‐low regions. In vivo, AHB Gel exhibits specific tumor‐targeting capacity with no fluorescence response in normal tissue, providing clear tumor boundaries. In addition, AHB Gel has good storage stability, which is conducive to its future clinical application. In summary, AHB Gel is a novel tumor microenvironment‐targeted DNA‐hybrid hydrogel for ATP‐based fluorescence imaging. It can enable the precise imaging of tumor tissues, showing promising application in fluorescence‐guided surgeries in the future.
FDA Approval Summary: Selpercatinib for the Treatment of Advanced <i>RET</i> Fusion-Positive Solid Tumors
Authors: Elizabeth S. Duke, Diana Bradford, Michelle Marcovitz, Anup K. Amatya, Pallavi S. Mishra-Kalyani, Emily Nguyen, Lauren S.L. Price, Jeanne Fourie Zirkelbach, Yangbing Li, Youwei Bi, Jeffrey Kraft, Sarah E. Dorff, Barbara Scepura, Maritsa Stephenson, Idara Ojofeitimi, Abhilasha Nair, Yu Han, Zivana Tezak, Steven J. Lemery, Richard Pazdur, Erin Larkins, Harpreet Singh
Journal: Clinical Cancer Research (2023)

On September 21, 2022, the U.S. Food and Drug Administration (FDA) granted accelerated approval to selpercatinib (Retevmo®, Eli Lilly and Company) for the treatment of adult patients with locally advanced or metastatic solid tumors with a rearranged during transfection (RET) gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options. The approval was based on data from Study LOXO-RET-17001 (LIBRETTO-001; NCT03157128), an international, non-randomized, multi-cohort clinical trial which included patients with advanced solid tumors harboring RET alterations. The overall response rate (ORR) in 41 patients with locally advanced or metastatic RET fusion-positive solid tumors other than non-small cell lung cancer (NSCLC) or thyroid cancer was 44% (95% CI: 28%, 60%) with median duration of response 24.5 months (95% CI: 9.2, not evaluable). Patients with 10 of 14 tumor types with a variety of fusion partners had objective responses, including patients with the following tumors: pancreatic adenocarcinoma, colorectal, salivary, unknown primary, breast, soft tissue sarcoma, bronchial carcinoid, ovarian, small intestine, and cholangiocarcinoma. The recommendation for approval was supported by results from LIBRETTO-001 in patients with RET fusion-positive NSCLC and thyroid cancer, which formed the basis of prior approvals in these tumor types. The most common adverse reactions (>25%) were edema, diarrhea, fatigue, dry mouth, hypertension, abdominal pain, constipation, rash, nausea, and headache. This is the first tissue agnostic approval of a RET-directed targeted therapy.
Kidney-Derived Thrombopoietin and Platelet Generation—A Proinflammatory Loop in CKD
Authors: Michael J. Hickey
Journal: Journal of the American Society of Nephrology (2023)

Centre for Inflammatory Diseases, Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia Correspondence: Dr. Michael J. Hickey, Centre for Inflammatory Diseases, Monash University Department of Medicine Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia. Email: [email protected] Published online ahead of print. Publication date available at www.jasn.org. See related article, "Thrombopoietin-Dependent Myelo-Megakaryopoiesis Fuels Thromboinflammation and Worsens Antibody-Mediated Chronic Renal Microvascular Injury," on pages 1207–1221.
Catheter Ablation Using Pulmonary Vein Isolation With vs Without Posterior Left Atrial Wall Isolation in Persistent AF—Reply
Authors: Peter M. Kistler, David Chieng, Jonathan M. Kalman
Journal: JAMA (2023)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Journals JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal